Peptide YY Research Articles

Exploring the Role of Metabolic Hormones in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive loss of motor neurons. Emerging evidence suggests a potential link between metabolic dysregulation and ALS pathogenesis. This study aimed to investigate the relationship between metabolic hormones and disease progression in ALS patients. A cross-sectional study was conducted involving 44 ALS patients recruited from a tertiary care center. Serum levels of insulin, total amylin, C-peptide, active ghrelin, GIP (gastric inhibitory peptide), GLP-1 active (glucagon-like peptide-1), glucagon, PYY (peptide YY), PP (pancreatic polypeptide), leptin, interleukin-6, MCP-1 (monocyte chemoattractant protein-1), and TNFα (tumor necrosis factor alpha) were measured, and correlations with ALSFRS-R, evolution scores, and biomarkers were analyzed using Spearman correlation coefficients. Subgroup analyses based on ALS subtypes, progression pattern of disease, and disease progression rate patterns were performed. Significant correlations were observed between metabolic hormones and ALS evolution scores. Insulin and amylin exhibited strong correlations with disease progression and clinical functional outcomes, with insulin showing particularly robust associations. Other hormones such as C-peptide, leptin, and GLP-1 also showed correlations with ALS progression and functional status. Subgroup analyses revealed differences in hormone levels based on sex and disease evolution patterns, with male patients showing higher amylin and glucagon levels. ALS patients with slower disease progression exhibited elevated levels of amylin and insulin. Our findings suggest a potential role for metabolic hormones in modulating ALS progression and functional outcomes. Further research is needed to elucidate the underlying mechanisms and explore the therapeutic implications of targeting metabolic pathways in ALS management.

Effects of semaglutide, Peptide YY3-36 and empagliflozin on metabolic dysfunction associated fatty steatotic liver disease in diet-induced obese rats with chronic nitric oxide synthase-inhibition

Effects of semaglutide, Peptide YY3-36 and empagliflozin on metabolic dysfunction associated fatty steatotic liver disease in diet-induced obese rats with chronic nitric oxide synthase-inhibition

Development of a Neuropeptide Y-Sensitive Implantable Microelectrode for Continuous Measurements.

In this work, we present the development of the first implantable aptamer-based platinum microelectrode for continuous measurement of a nonelectroactive molecule, neuropeptide Y (NPY). The aptamer immobilization was performed via conjugation chemistry and characterized using cyclic voltammetry before and after the surface modification. The redox label, methylene blue (MB), was attached at the end of the aptamer sequence and characterized using square wave voltammetry (SWV). NPY standard solutions in a three-electrode cell were used to test three aptamers in steady-state measurement using SWV for optimization. The aptamer with the best performance in the steady-state measurements was chosen, and continuous measurements were performed in a flow cell system using intermittent pulse amperometry. Dynamic measurements were compared against confounding and similar peptides such as pancreatic polypeptide and peptide YY, as well as somatostatin to determine the selectivity in the same modified microelectrode. Our Pt-microelectrode aptamer-based NPY biosensor provides signals 10 times higher for NPY compared to the confounding molecules. This proof-of-concept shows the first potential implantable microelectrode that is selectively sensitive to NPY concentration changes.

Trajectory of Ghrelin and PYY Around a Test Meal in Males and Females with Avoidant/Restrictive Food Intake Disorder Versus Healthy Controls

Disruptions in appetite-regulating hormones may contribute to the development and/or maintenance of avoidant/restrictive food intake disorder (ARFID). No study has previously assessed fasting levels of orexigenic ghrelin or anorexigenic peptide YY (PYY), nor their trajectory in response to food intake among youth with ARFID across the weight spectrum. We measured fasting and postprandial (30, 60, 120minutes post-meal) levels of ghrelin and PYY among 127 males and females with full and subthreshold ARFID (n = 95) and healthy controls (HC; n = 32). We used latent growth curve analyses to examine differences in the trajectories of ghrelin and PYY between ARFID and HC. Fasting levels of ghrelin did not differ in ARFID compared to HC. Among ARFID, ghrelin levels declined more gradually than among HC in the first hour post meal (p =.005), but continued to decline between 60 and 120minutes post meal, whereas HC plateaued (p =.005). Fasting and PYY trajectory did not differ by group. Findings did not change after adjusting for BMI percentile (M(SD)ARFID = 37(35); M(SD)HC = 53(26); p =.006) or calories consumed during the test meal (M(SD)ARFID = 294(118); M(SD)HC = 384 (48); p <.001). These data highlight a distinct trajectory of ghrelin following a test meal in youth with ARFID. Future research should examine ghrelin dysfunction as an etiological or maintenance factor of ARFID.

Effect of gut hormones on bone metabolism and their possible mechanisms in the treatment of osteoporosis.

Bone is a highly dynamic organ that changes with the daily circadian rhythm. During the day, bone resorption is suppressed due to eating, while it increases at night. This circadian rhythm of the skeleton is regulated by gut hormones. Until now, gut hormones that have been found to affect skeletal homeostasis include glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP), and peptide YY (PYY), which exerts its effects by binding to its cognate receptors (GLP-1R, GLP-2R, GIPR, and Y1R). Several studies have shown that GLP-1, GLP-2, and GIP all inhibit bone resorption, while GIP also promotes bone formation. Notably, PYY has a strong bone resorption-promoting effect. In addition, gut microbiota (GM) plays an important role in maintaining bone homeostasis. This review outlines the roles of GLP-1, GLP-2, GIP, and PYY in bone metabolism and discusses the roles of gut hormones and the GM in regulating bone homeostasis and their potential mechanisms.

Evidence of Nesfatin-1 in Mouse Intestinal Enteroendocrine Cells

Objectives: Post-prandial insulin secretion is predominantly regulated by four intestinal hormones: glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), Cholecystokinin (CCK) and peptide YY (PYY). Nesfatin-1, an insulinotropic and anorexigenic secreted peptide was reported in mouse hypothalamus. Data supporting nesfatin-1 expression in intestine is minimal. Is nesfatin-1 expressed in mouse intestinal cells? Does it affect intestinal hormones known to stimulate or inhibit insulin secretion? We present STC-1 cells as viable in vitro models to study nesfatin-1’s biological action in intestine.       Methods: Immunofluorescence histochemistry (IHC) of intestinal sections from male C57BL/6 mice were carried out. STC-1 cells (n=8 wells/treatment) were dose-dependently treated with nesfatin-1, followed by RT-qPCR and immunoassay (ELISA) respectively. One-Way ANOVA followed by Tukey’s multiple comparison test using GraphPad Prism software was used for data analysis. p&lt;0.01 was considered statistically significant.       Results: IHC showed NUCB2/nesfatin-1 co-localizing CCK, PYY and GLP-1 in the intestinal mucosa of mice. Static incubation of STC-1 cells with nesfatin-1 upregulated both CCK, PYY and GLP-1 mRNA expression (1 and 10nM) and secretion at 1 hr post-incubation (0.1, 1 and 10nM). Conversely, nesfatin-1 downregulated PYY mRNA expression and secretion in STC-1 cells (all doses tested).       Conclusion: The current data shows cell-specific localization of nesfatin-1 in the intestinal mucosa and establishes STC-1 cells as in vitro models to study nesfatin-1. This study adds a novel function for intestinal nesfatin-1 in stimulating insulinotropic intestinal hormones (GLP-1, GIP, CCK) and inhibit PYY which is insulinostatic.

Whole-Body Loss of NUCB2/Nesfatin-1 Alters Enteric Hormone Expression

Objectives: Post-prandial insulin secretion is predominantly regulated by four intestinal hormones: glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) [collectively called incretins], Cholecystokinin (CCK) and peptide YY (PYY). Nesfatin-1, an insulinotropic and anorexigenic secreted peptide encoded by nucleobindin-2 (NUCB2) was reported in the mouse hypothalamus. We have earlier reported that nesfatin-1 stimulates incretins and CCK expression and secretion while being a potent inhibitor of PYY expression, both in vitro and vivo. We further this observation in this abstract by testing the incretin, CCK, and PYY expression in a mouse model of global Nesfatin-1/NUCB2 knockout (NKO).       Methods: For the current study 6-8 weeks old male NKO mice and age-matched littermate C57BL/6J mice were used as controls (n=7). Total RNA extraction followed by Real-Time quantitative PCR (RT-qPCR) of small/large intestine samples was carried out. One-way ANOVA followed by Tukey’s multiple comparison test using GraphPad Prism software was used for data analysis. p&lt;0.01 was considered statistically significant.       Results: We found that whole-body knockout of NUCB2/Nesfatin-1 downregulated large and small intestinal expression of incretins, CCK, and increased expression of PYY.       Conclusion: The current data extends our earlier observation in a mouse model lacking nesfatin-1. Lack of nesfatin-1 affects the healthy expression of incretins, CCK, and PYY in the intestine. These results highlight the importance of endogenous nesfatin-1 and its role in energy balance by modulating crucial enteroendocrine hormones known for their role in energy balance.       Source of Support: Dr. Unniappan's lab (University of Saskatchewan) and Canadian Institutes of Health Research (CIHR).

Associations of adupocutokine and metaboliv hormone level in young people aged 25-44 years with type 2 diabetes mellitus and abdominal obesity

BACKGROUND: Diabetes mellitus and obesity are two closely related diseases that are a global public health problem. Obesity is characterized by an increase in the volume of adipose tissue and a change in the production and function of adipocytokines, which leads to a violation of the regulation of insulin sensitivity and glucose metabolism, contributing to the development of insulin resistance and diabetic pathology.AIM: The aim of this study was to evaluate the concentrations of individual adipocytokines and metabolic hormones in patients with DM2 and without diabetes, depending on the presence/absence of abdominal obesity (AO).MATERIALS AND METHODS: A single-center observational cross-sectional study was conducted. A population subsample of men and women aged 25–44 years was examined. Socio-demographic data were collected, anthropometric measurements were performed. The levels of amylin, C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 (GLP-1), glucagon, were determined in blood serum by multiplex analysis using a set of reagents Human Metabolic Hormone V3 (USA) and Human Adipokine Panel 1 (USA) on a Luminex MAGPIX flow fluorimeter (USA). interleukin 6, insulin, leptin, monocytic chemotactic factor 1 (MCP-1), pancreatic polypeptide (PP), peptide YY (PYY), tumor necrosis factor alpha (TNF-α), adiponectin, adipsin, lipocalin-2, plasminogen activator inhibitor-1 (PAI-1) and resistin.RESULTS: The study included 105 people. The main group consisted of 35 people with diabetes mellitus, 11 of them without AO and 24 with AO, the control group consisted of 70 people without diabetes mellitus (35 people with AO and 35 without AO), comparable in gender and age with the main group. In individuals with abdominal obesity, regardless of the presence of type 2 diabetes mellitus, the levels of C-peptide, GLP-1, insulin, leptin and TNF-alpha are higher than in individuals without abdominal obesity. The chance of having diabetes mellitus and AO is associated with an increase in leptin levels (OR=1.367, 95% CI: 1.050–1.779, p=0.020).CONCLUSION: The results of our study show that the indicators of the adipocytokine profile differ significantly in individuals with the presence/absence of abdominal obesity. According to our data, leptin makes the greatest contribution to the development of SD2 against the background of AO. Further research is needed to identify causal relationships and determine whether treatment that regulates adipocytokine levels can help in personalized approaches to the prevention and treatment of type 2 diabetes mellitus.

Substituting carbohydrate at lunch for added protein increases fat oxidation during subsequent exercise in healthy males.

How pre-exercise meal composition influences metabolic and health responses to exercise later in the day is currently unclear. Examine the effects of substituting carbohydrate for protein at lunch on subsequent exercise metabolism, appetite, and energy intake. Twelve healthy males completed three trials in randomized, counterbalanced order. Following a standardized breakfast (779 ± 66 kcal; ∼08:15), participants consumed a lunch (1186 ± 140 kcal; ∼13:15) containing either 0.2 g·kg-1 carbohydrate and ∼2 g·kg-1 protein (LO-CARB), 2 g·kg-1 carbohydrate and ∼0.4 g·kg-1 protein (HI-CARB), or fasted (FAST). Participants later cycled at ∼60% V̇O2peak for 1 h (∼16:15) and post-exercise ad-libitum energy intake was measured (∼18:30). Substrate oxidation, subjective appetite, and plasma concentrations of glucose, insulin, non-esterified fatty acids (NEFA), peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and acylated ghrelin (AG) were measured for 5 h post-lunch. Fat oxidation was greater during FAST (+11.66 ± 6.63 g) and LO-CARB (+8.00 ± 3.83 g) than HI-CARB (p < 0.001), with FAST greater than LO-CARB (+3.67 ± 5.07 g; p < 0.05). NEFA were lowest in HI-CARB and highest in FAST, with insulin demonstrating the inverse response (all p < 0.01). PYY and GLP-1 demonstrated a stepwise pattern, with LO-CARB greatest and FAST lowest (all p < 0.01). AG was lower during HI-CARB and LO-CARB versus FAST (p < 0.01). Energy intake in LO-CARB was lower than FAST (-383 ± 233 kcal; p < 0.001) and HI-CARB (-313 ± 284 kcal; p < 0.001). Substituting carbohydrate for protein in a pre-exercise lunch increased fat oxidation, suppressed subjective and hormonal appetite, and reduced post-exercise energy intake.

Exploring the impact of lifestyle and environmental exposures on appetite hormone levels in children and adolescents: An observational study

BackgroundAppetite hormones are considered a promising target in fighting obesity as impaired appetite hormone levels have already been associated with obesity. However, further insights in the drivers of appetite hormone levels are needed. ObjectivesIn this study, we investigated the associations of fasting appetite hormone levels with lifestyle and environmental exposures in children and adolescents. MethodsA total of 534 fasting blood samples were collected from children and adolescents (4-16y,50% boys) and appetite hormone levels (glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide (PP), leptin and ghrelin) were measured. Exposures included dietary quality (fiber-rich food intake, sugar propensity, fat propensity), psychosocial stress (happiness, negative emotions, negative life events and emotional problems), sleep duration, physical activity and environmental quality (long term black carbon (BC), particulate matter <2.5 μM (PM2.5), nitrogen dioxide (NO2) exposure, and green space in a 100 m and 2000 m radius around the residence). A multi-exposure score was calculated to combine all the exposures at study in one measure. Associations of individual exposures and multi-exposure score with appetite hormone levels were evaluated using linear mixed regression models adjusting for sex, age, socioeconomic status, waist-to-height ratio and multiple testing. ResultsGLP-1 was associated with air pollution exposure (NO2 β* = -0.13, BC β* = -0.15, PM2.5 β* = -0.16, all p < 0.001). Leptin was associated with green space in a 100 m radius around the residence (β* = -0.11; p = 0.002). Ghrelin was associated with negative emotions (active ghrelin β* = -0.16; p = 0.04, total ghrelin β* = -0.23; p = 0.0051) and happiness (active ghrelin β* = 0.25; p < 0.001, total ghrelin β* = 0.26; p < 0.001). Furthermore, total ghrelin levels were associated with the multi-exposure score, reflecting unhealthy exposures and lifestyle (β* = -0.22; p = 0.036). DiscussionOur findings provide new insights into the associations of exposures with appetite hormone levels, which are of high interest for preventive obesity research. Further research is crucial to reveal the underlying mechanisms of the observed associations.

Mechanisms underlying the gut-brain communication: How enterochromaffin (EC) cells activate vagal afferent nerve endings in the small intestine.

How the gastrointestinal tract communicates with the brain, via sensory nerves, is of significant interest for our understanding of human health and disease. Enterochromaffin (EC) cells in the gut mucosa release a variety of neurochemicals, including the largest quantity of 5-hydroxytryptamine (5-HT) in the body. How 5-HT and other substances released from EC cells activate sensory nerve endings in the gut wall remains a major unresolved mystery. We used in vivo anterograde tracing from nodose ganglia to determine the spatial relationship between 5-HT synthesizing and peptide-YY (PYY)-synthesizing EC cells and their proximity to vagal afferent nerve endings that project to the mucosa of mouse small intestine. The shortest mean distances between single 5-HT- and PYY-synthesizing EC cells and the nearest vagal afferent nerve endings in the mucosa were 33.1±14.4µm (n=56; N=6) and 70.3±32.3µm (n=16; N=6). No morphological evidence was found to suggest that 5-HT- or PYY-containing EC cells form close morphological associations with vagal afferents endings, or varicose axons of passage. The large distances between EC cells and vagal afferent endings are many hundreds of times greater than those known to underlie synaptic transmission in the nervous system (typically 10-15nm). Taken together, the findings lead to the inescapable conclusion that communication between 5-HT-containing EC cells and vagal afferent nerve endings in the mucosa of the mouse small intestinal occurs in a paracrine fashion, via diffusion. New and Noteworthy None of the findings here are consistent with a view that close physical contacts occur between 5-HT-containing EC cells and vagal afferent nerve endings in mouse small intestine. Rather, the findings suggest that gut-brain communication between EC cells and vagal afferent endings occurs via passive diffusion. The morphological data presented do not support the view that EC cells are physically close enough to vagal afferent endings to communicate via fast synaptic transmission.

Acid-base properties of non-protein nitrogen affect nutrients intake, rumen fermentation and antioxidant capacity of fattening Hu sheep.

This study conducted a comparison of the effects of non-protein nitrogen with different acid-base properties on feed intake, rumen fermentation, nutrient digestion and antioxidant capacity in fattening Hu sheep. Sixteen fattening male sheep (31.43 ± 2.41 kg) with permanent rumen cannulas were randomly assigned to two dietary treatments: 1% urea and 1.78% ammonium chloride (NH4Cl, AC). A 42 days experimental period was conducted, with 14 days for adaptation and 28 days for treatment. Daily feed intake was recorded and various samples including feed, feces, rumen fluid, and blood were collected at different time points during the final week. The results indicated that the urea group had significantly higher dry matter intake, average daily gain, and gain efficiency in comparison to the AC group (p < 0.01). There was no difference in rumen pH and concentration of ammonia nitrogen between different groups (p > 0.05), but the rumen pH of urea group was higher than that of the AC group at 1 and 3 h after feeding (p < 0.05). The urea group exhibited higher concentrations of total volatile fatty acids (VFA) and individual VFAs compared to the AC group at all-time points (p < 0.01). Compared to the urea group, the intake of all nutrients decreased in the AC group (p < 0.01), but the digestibility of dry matter and organic matter increased significantly (p < 0.01), and the digestibility of CP had an increasing trend (p = 0.06) in the AC group. Additionally, the urea group had lower levels of serum glucagon-like peptide-1, peptide YY, Cl, total protein and globulin than the AC group (p < 0.05). The overall levels of HCO3-, superoxide dismutase, glutathione peroxidase, catalase, albumin/globulin, blood urea nitrogen and total cholesterol in the urea group increased significantly compared to the AC group (p < 0.05). It was concluded that adding urea to the high-concentrate diet resulted in increased rumen pH and improved rumen fermentation and growth performance in fattening sheep compared to NH4Cl addition. Furthermore, urea addition improved sheep's antioxidant capacity and maintained their acid-base balance more effectively as compared to NH4Cl.

Gut hormones and appetite regulation.

Various gut hormones interact with the brain through delicate communication, thereby influencing appetite and subsequent changes in body weight. This review summarizes the effects of gut hormones on appetite, with a focus on recent research. Ghrelin is known as an orexigenic hormone, whereas glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), postprandial peptide YY (PYY), and oxyntomodulin (OXM) are known as anorexigenic hormones. Recent human studies have revealed that gut hormones act differently in various systems, including adipose tissue, beyond appetite and energy intake, and even involve in high-order thinking. Environmental factors including meal schedule, food contents and quality, type of exercise, and sleep deprivation also play a role in the influence of gut hormone on appetite, weight change, and obesity. Recently published studies have shown that retatrutide, a triple-agonist of GLP-1, GIP, and glucagon receptor, and orforglipron, a GLP-1 receptor partial agonist, are effective in weight loss and improving various metabolic parameters associated with obesity. Various gut hormones influence appetite, and several drugs targeting these receptors have been reported to exert positive effects on weight loss in humans. Given that diverse dietary and environmental factors affect the actions of gut hormones and appetite, there is a need for integrated and largescale long-term studies in this field.

Intestinal Acyl-CoA synthetase 5 (ACSL5) deficiency potentiates postprandial GLP-1 & PYY secretion, reduces food intake, and protects against diet-induced obesity

ObjectiveIn the small intestine, the products of digestion of dietary triacylglycerol (TAG), fatty acids (FA) and monoacylglycerol, are taken up by absorptive cells, enterocytes, for systemic energy delivery. These digestion products can also bind receptors on endocrine cells to stimulate the release of hormones capable of influencing systemic energy metabolism. The initial phase of intestinal FA absorption involves the acylation of FAs to acyl-CoA by the acyl-CoA long chain synthetase (ACSL) enzymes. ACSL5 is abundantly expressed in the small intestinal epithelium where it is the major ACSL isoform, contributing approximately 80% of total ACSL activity. In mice with whole body deficiency of ACSL5, the rate of dietary fat absorption is reduced and energy expenditure is increased. However, the mechanisms by which intestinal ACSL5 contributes to intestinal FA metabolism, enteroendocrine signaling, and regulation of energy expenditure remain undefined. Here, we test the hypothesis that intestinal ACSL5 regulates energy metabolism by influencing dietary fat absorption and enteroendocrine signaling. MethodsTo explore the role of intestinal ACSL5 in energy balance and intestinal dietary fat absorption, a novel mouse model of intestine specific ACSL5 deficiency (ACSL5IKO) was generated by breeding ACSL5 floxed (ACSL5loxP/loxP) to mice harboring the tamoxifen inducible, villin-Cre recombinase. ACSL5IKO and control, ACSL5loxP/loxP mice were fed chow (low in fat) or a 60% high fat diet (HFD), and metabolic phenotyping was performed including, body weight, body composition, insulin and glucose tolerance tests, energy expenditure, physical activity, and food intake studies. Pair-feeding studies were performed to determine the role of food intake in regulating development of obesity. Studies of dietary fat absorption, fecal lipid excretion, intestinal mucosal FA content, and circulating levels of glucagon like peptide 1 (GLP-1) and peptide YY (PYY) in response to a TAG challenge were performed. Treatment with a GLP-1 receptor antagonist was performed to determine the contribution of GLP-1 to acute regulation of food intake. ResultsWe found that ACSL5IKO mice experienced rapid and sustained protection from body weight and fat mass accumulation during HFD feeding. While intestine specific deficiency of ACSL5 delayed gastric emptying and reduced dietary fat secretion, it did not result in increased excretion of dietary lipid in feces. Energy expenditure and physical activity were not increased in ACSL5IKO mice. Mice deficient in intestinal ACSL5 display significantly reduced energy intake during HFD, but not chow feeding. When HFD intake of control mice was matched to ACSL5IKO during pair-feeding studies, no differences in body weight or fat mass gain were observed between groups. Postprandial GLP-1 and PYY were significantly elevated in ACSL5IKO mice secondary to increased FA content in the distal small intestine. Blockade of GLP-1 signaling by administration of a long-acting GLP-1 receptor antagonist partially restored HFD intake of ACSL5IKO. ConclusionsThese data indicate that intestinal ACSL5 serves as a critical regulator of energy balance, protecting mice from diet-induced obesity exclusively by increasing satiety and reducing food intake during HFD feeding. The reduction in food intake observed in ACSL5IKO mice is driven, in part, by increased postprandial GLP-1 and PYY secretion. These effects are only observed during HFD feeding, suggesting that altered processing of dietary fat following intestinal ACSL5 ablation contributes to GLP-1 and PYY mediated increases in satiety.

Fasting and post prandial pancreatic and enteroendocrine hormone levels in obese and non-obese participants

Circulating insulin levels are known to be increased in people with higher body mass index (BMI) due to effects of adiposity on insulin resistance, whilst gut hormones have a more complex relationship, with fasting peptideYY (PYY) reported to be inversely related to BMI. This study aimed to further explore fasting and post prandial pancreatic and gut hormone concentrations in plasma samples from obese and non-obese participants. Participants with healthy BMI (n=15), overweight BMI (n=29) and obesity (n=161) had samples taken fasting and 30 min post mixed liquid meal for analysis of glucagon-like peptide-1 (GLP-1), PYY, glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon. Data visualiation used linear discriminant analysis for dimensionality reduction, to visualise the data and assess scaling of each hormone. Fasting levels of insulin, GIP and PYY were shown to be key classifiers between the 3 groups on ANCOVA analysis, with an observation of increased GIP levels in overweight, but not obese participants. In non-obese subjects, fasting GIP, PYY and insulin correlated with BMI, whereas in subjects with obesity only the pancreatic hormones glucagon and insulin correlated with BMI. Concentrations of total GLP-1 in the fasting state correlated strongly with glucagon levels, highlighting potential assay cross-reactivities. The study, which included a relatively large number of subjects with severe obesity, supported previous evidence of BMI correlating negatively with fasting PYY and positively with fasting insulin. The observation of increased fasting GIP levels in overweight but not obese participants deserves further validation and mechanistic investigation.

Effect of inulin on breath hydrogen, postprandial glycemia, gut hormone release, and appetite perception in RYGB patients: a prospective, randomized, cross-over pilot study

Background and objectiveLarge intestinal fermentation of dietary fiber may control meal-related glycemia and appetite via the production of short-chain fatty acids (SCFA) and the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). We investigated whether this mechanism contributes to the efficacy of the Roux-en-Y gastric bypass (RYGB) by assessing the effect of oligofructose-enriched inulin (inulin) vs. maltodextrin (MDX) on breath hydrogen (a marker of intestinal fermentation), plasma SCFAs, gut hormones, insulin and blood glucose concentrations as well as appetite in RYGB patients.MethodEight RYGB patients were studied on two occasions before and ~8 months after surgery using a cross-over design. Each patient received 300 ml orange juice containing 25 g inulin or an equicaloric load of 15.5 g MDX after an overnight fast followed by a fixed portion snack served 3 h postprandially. Blood samples were collected over 5 h and breath hydrogen measured as well as appetite assessed using visual analog scales.ResultsSurgery increased postprandial secretion of GLP-1 and PYY (P ≤ 0.05); lowered blood glucose and plasma insulin increments (P ≤ 0.05) and reduced appetite ratings in response to both inulin and MDX. The effect of inulin on breath hydrogen was accelerated after surgery with an increase that was earlier in onset (2.5 h vs. 3 h, P ≤ 0.05), but less pronounced in magnitude. There was, however, no effect of inulin on plasma SCFAs or plasma GLP-1 and PYY after the snack at 3 h, neither before nor after surgery. Interestingly, inulin appeared to further potentiate the early-phase glucose-lowering and second-meal (3–5 h) appetite-suppressive effect of surgery with the latter showing a strong correlation with early-phase breath hydrogen concentrations.ConclusionRYGB surgery accelerates large intestinal fermentation of inulin, however, without measurable effects on plasma SCFAs or plasma GLP-1 and PYY. The glucose-lowering and appetite-suppressive effects of surgery appear to be potentiated with inulin.

Zhuang-Gu-Fang intervenes vasculogenic and osteogenic coupling in GK rats through Notch1/Noggin/VEGF pathway

BackgroundZhuang-Gu-Fang (ZGF) has been proved to treat osteoporosis in ovariectomized rats by increasing osteogenic related factors Leptin, Ghrelin and Peptide YY(PYY). However, the mechanism of ZGF in the treatment of diabetic osteoporosis (DOP) remains unclear. The aim of this study was to explore the therapeutic effect of ZGF on DOP and its potential molecular mechanism. MethodsUsing GK rats as models, the pharmacodynamic effects of ZGF on bone loss were evaluated by hematoxylin-eosin (H&E) staining and micro-computed.tomography (micro-CT). The expression levels of CD31 and endomucin (Emcn) were detected by immunofluorescence to assess the role of ZGF in angiogenic osteogenic coupling. Finally, real-time quantitative PCR (RT-PCR) and Western Blot (WB)were used to detect the expression levels of osteogenic and angiogenesis-related genes and proteins Notch1, Noggin and vascular endothelial growth factor (VEGF). ResultsAdministration of ZGF demonstrated a significant mitigation of bone loss attributable to elevated glucose levels. H&E staining and micro-CT showed that ZGF notably improved the integrity of the trabecular and cortical bone microarchitecture. Moreover, ZGF was found to augment the density of type H vessels within the bone tissue, alongside elevating the expression levels of Osterix, a transcription factor pivotal for bone formation. Furthermore, our findings suggest that ZGF facilitates the activation of the Notch1/Noggin/VEGF pathway, indicating a potential mechanism through which ZGF exerts its osteoprotective effects. ConclusionOur results suggest that ZGF potentially facilitates the formation of type H vessels through the Notch1/Noggin/VEGF pathway. This action not only enhances angiogenic-osteogenic coupling but also contributes to the improvement of bone structure and density. Consequently, ZGF emerges as a promising therapeutic agent for the prevention and management of DOP, offering a novel approach by leveraging angiogenesis-dependent osteogenesis.

Illuminating the neuropeptide Y4 receptor and its ligand pancreatic polypeptide from a structural, functional, and therapeutic perspective

The neuropeptide Y4 receptor (Y4R), a rhodopsin-like G protein-coupled receptor (GPCR) and the hormone pancreatic polypeptide (PP) are members of the neuropeptide Y family consisting of four receptors (Y1R, Y2R, Y4R, Y5R) and three highly homologous peptide ligands (neuropeptide Y, peptide YY, PP). In this family, the Y4R is of particular interest as it is the only subtype with high affinity to PP over NPY. The Y4R, as a mediator of PP signaling, has a pivotal role in appetite regulation and energy homeostasis, offering potential avenues for the treatment of metabolic disorders such as obesity. PP as anorexigenic peptide is released postprandial from the pancreas in response to food intake, induces satiety signals and contributes to hamper excessive food intake. Moreover, this system was also described to be associated with different types of cancer: overexpression of Y4R have been found in human adenocarcinoma cells, while elevated levels of PP are related to the development of pancreatic endocrine tumors. The pharmacological relevance of the Y4R advanced the search for potent and selective ligands for this receptor subtype, which will be significantly progressed through the elucidation of the active state PP-Y4R cryo-EM structure. This review summarizes the development of novel PP-derived ligands, like Obinepitide as dual Y2R/Y4R agonist in clinical trials or UR-AK86c as small hexapeptide agonist with picomolar affinity, as well as the first allosteric modulators that selectively target the Y4R, e.g. VU0506013 as potent Y4R positive allosteric modulator or (S)-VU0637120 as allosteric antagonist. Here, we provide valuable insights into the complex physiological functions of the Y4R and PP and the pharmacological relevance of the system in appetite regulation to open up new avenues for the development of tool compounds for targeted therapies with potential applications in metabolic disorders.

Proteomics of appetite-regulating system influenced by menstrual cycle and intensive exercise in female athletes: a pilot study

Female athletes who endure intense training are at risk of developing the 'female athlete triad,' making energy intake management crucial. However, the fluctuations in estradiol and progesterone levels throughout the menstrual cycle present a challenge in maintaining consistent energy intake. This study aimed to uncover the underlying factors associated with appetite regulation linked to menstrual phases and exercise using proteomic approach. Five female athletes engaged in 60 min of bicycle exercise, followed by 90 min of rest, during both the follicular and luteal phases. Serum samples were collected before, during, and after exercise, and the serum proteome was analyzed using 2D-gel electrophoresis. A total of 511 spots were detected in the subjects' serum profiles, with significant decreases observed in haptoglobin during the luteal phase and complement component 3 during bicycle training. Unsupervised learning with a generalized estimating equation analysis showed that serum peptide YY (PYY), an appetite suppressor, significantly influenced the fluctuations of serum proteins induced by exercise (p < 0.05). Regression analysis demonstrated a positive correlation between PYY and serum IgM (R = 0.87), implying that the intestinal environment and the immune response in female athletes may contribute to appetite regulation.

Fermented bamboo powder activates gut odorant receptors, and promotes intestinal health and growth performance of dwarf yellow-feathered broiler chickens

The present study investigated the effects of fermented bamboo powder (FPB) on gut odorant receptors (OR), intestinal health, and growth performance of dwarf yellow-feathered broiler chickens. Six hundred (600) healthy 1-day-old chicks were randomly assigned into 2 groups, with 10 replicates consisting of 30 chicks each. The control group was fed a basal diet. In contrast, the experimental group was fed the basal diet supplemented with 1.0, 2.0, 4.0, and 6.0 g/kg FBP for 4 different phases, namely phase I (1-22 d), phase II (23-45 d), phase III (46-60 d), and phase IV (61-77 d), respectively. The first 2 phases were considered pretreatment (0-45 d), and the remaining were experimental (46-77 d) periods. The tissue samples were collected from phase IV. The chickens in the FBP supplementation group exhibited a significant increment in body weight gain, evisceration yield, breast, thigh, and liver weight, while also experiencing a decrease in the FCR (P < 0.05). Furthermore, the villus height, crypt depth, and villus area exhibited significant increases in the FBP group (P < 0.01). Additionally, the secretion levels of gut hormones such as glucagon-like peptide-1, peptide YY, cholecystokinin, and 5-hydroxytryptamine were significantly elevated in the serum, duodenum, jejunum, and ileum tissues in the FBP group (P < 0.05). The results of qRT-PCR indicated that ORs had responsive expression in the gizzard, proventriculus, and small intestine of chickens when fed with the FBP diet (P < 0.05). Notably, the expression of the COR1, COR2, COR4, COR6, COR8, COR9, OR52R1, OR51M1, OR1F2P, OR5AP2, and OR14J1L112 genes was stronger in the small intestines compared to the gizzard and proventriculus. In conclusion, these results suggest that the FPB plays a crucial role in growth performance, activation of ORs, and gut health and development.